Concordance of Drug-resistance Profiles Between Persons With Drug-resistant Tuberculosis and Their Household Contacts: A Systematic Review and Meta-analysis

Abstract

Background: Household contacts of patients with drug-resistant tuberculosis (TB) are at high risk for being infected with Mycobacterium tuberculosis and for developing TB disease. To guide regimen composition for the empirical treatment of TB infection and disease in these household contacts, we estimated drug-resistance profile concordance between index patients with drug-resistant TB and their household contacts.

Methods: We performed a systematic review and meta-analysis of studies published through 24 July 2018 that reported resistance profiles of drug-resistant TB index cases and secondary cases within their households. Using a random-effects meta-analysis, we estimated resistance profile concordance, defined as the percentage of secondary cases whose M. tuberculosis strains were resistant to the same drugs as strains from their index cases. We also estimated isoniazid/rifampin concordance, defined as whether index and secondary cases had identical susceptibilities for isoniazid and rifampin only.

Results: We identified 33 eligible studies that evaluated resistance profile concordance between 484 secondary cases and their household index cases. Pooled resistance profile concordance was 54.3% (95% confidence interval [CI], 40.7-67.6%; I2 = 85%). Pooled isoniazid/rifampin concordance was 82.6% (95% CI, 72.3-90.9%; I2 = 73%). Concordance estimates were similar in a subanalysis of 16 studies from high-TB-burden countries. There were insufficient data to perform a subanalysis among pediatric secondary cases.

Conclusions: Household contacts of patients with drug-resistant TB should receive treatment for TB infection and disease that assumes that they, too, are infected with a drug-resistant M. tuberculosis strain. Whenever possible, drug susceptibility testing should be performed for secondary cases to optimize regimen composition.

Keywords: Mycobacterium tuberculosis genotyping; tuberculosis contact investigation; tuberculosis prevention and control; tuberculosis transmission.

Figure 1.

Search strategy. Abbreviations: DR-TB, drug-resistant tuberculosis; DST, drug susceptibility test; WHO GIM, World Health Organization Global Index Medicus; WoS, Web of Science.

Figure 2.

Forest plot of resistance profile concordance in the 33 included studies. Abbreviations: CDC, Centers for Disease Control and Prevention; CI, confidence interval; WHO, World Health Organization.

Figure 3.

Forest plot of isoniazid/rifampin concordance. Abbreviations: CDC, Centers for Disease Control and Prevention; CI, confidence interval.

Figure 4.

Forest plot of resistance profile concordance in high-TB-incidence countries. Countries were classified as having a high TB incidence if the WHO estimated their 2017 TB incidence to be >100 per 100 000 population [11]. Abbreviations: CDC, Centers for Disease Control and Prevention; CI, confidence interval; TB, tuberculosis; WHO, World Health Organization.

Figure 5.

Forest plot of isoniazid/rifampin concordance in high-TB-incidence countries. Countries were classified as having a high TB incidence if the WHO estimated their 2017 tuberculosis incidence to be >100 per 100 000 population [11]. Abbreviations: CDC, Centers for Disease Control and Prevention; CI, confidence interval; TB, tuberculosis; WHO, World Health Organization.

Figure 6.

Forest plot of resistance profile concordance among co-prevalent secondary cases and their index cases. Abbreviations: CDC, Centers for Disease Control and Prevention; CI, confidence interval; TB, tuberculosis; WHO, World Health Organization.

Figure 7.

Forest plot of isoniazid/rifampin concordance for co-prevalent secondary cases and their index cases. Abbreviations: CDC, Centers for Disease Control and Prevention; CI, confidence interval.